Control of DNA Damage Bypass by Ubiquitylation of PCNA

Brittany M. Ripley; Melissa S. Gildenberg; M. Todd Washington

doi:10.3390/genes11020138

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Control of DNA Damage Bypass by Ubiquitylation of PCNA

Journal article

Open access

Peer reviewed

Control of DNA Damage Bypass by Ubiquitylation of PCNA

Brittany M. Ripley, Melissa S. Gildenberg and M. Todd Washington

Genes, Vol.11(2), p.138

02/01/2020

DOI: 10.3390/genes11020138

PMCID: PMC7074500

PMID: 32013080

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Abstract

DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways.

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Control of DNA Damage Bypass by Ubiquitylation of PCNA
Creators: Brittany M. Ripley - University of Iowa
Melissa S. Gildenberg - University of Iowa
M. Todd Washington - University of Iowa
Resource Type: Journal article
Publication Details: Genes, Vol.11(2), p.138
DOI: 10.3390/genes11020138
PMID: 32013080
PMCID: PMC7074500
NLM abbreviation: Genes (Basel)
ISSN: 2073-4425
eISSN: 2073-4425
Publisher: Mdpi
Number of pages: 15
Grant note: GM081433 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
Language: English
Date published: 02/01/2020
Academic Unit: Microbiology and Immunology; Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984288728002771

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